Lipocalin 2 promotes the migration and invasion of esophageal squamous cell carcinoma cells through a novel positive feedback loop

Du, Zhifeng; Wu, Bing‐Li; Xie, Yang‐Min; Zhang, Yingli; Liao, Lian‐Di; Zhou, Fei; Xie, Jian‐Jun; Zeng, Fa‐Min; Xu, Xiu‐E; Fang, Wang‐Kai; Li, En‐Min; Xu, Li‐Yan

doi:10.1016/j.bbamcr.2015.07.007

Cited by 33 publications

(44 citation statements)

References 36 publications

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“…Elevated expression of NGAL can increase the invasiveness of certain cancer cells, while inhibition of NGAL expression decreases their invasiveness and metastasis [81,91,96,97]. New approaches to target MMP-9/NGAL are needed as MMP-9 inhibitors have not performed well in clinical cancer trials [98].…”

Section: Effects Of Ngal On Cancer Progressionmentioning

confidence: 99%

“…Many transcription factors, including the estrogen and androgen receptors, regulate NGAL expression by both positive and negative mechanisms [67][68][69][70][71][72][73][74][75][76][77]. 11 NGAL is an important molecule in many different types of cancer including: breast [9,10,77], colorectal (CRC) [78,79], endometrial [80], esophageal [7,81], gastric cancer [6], liver [82][83][84], lung [85][86][87] ovarian [88], pancreatic [89,90], prostate [76,91], renal [8,92] and thyroid cancer [68]. In general, elevated NGAL expression has been associated with advanced cancer and poor prognosis.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…This may be a part of the mechanism of increased invasiveness of the ESCC cells. Thus in ESCC cells, NGAL may increase migration and invasion by a positive feedback loop[81].Radiation is frequently used to treat patients with oral cancers. By performing DNA microarray analysis after radiation treatment of Ca9-22 oral cancer cells, it was determined that NGAL had the highest increase in expression out of a total of 167 genes that showed elevated expression in irradiated vs non-irradiated cells.…”

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confidence: 99%

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Roles of NGAL and MMP-9 in the tumor microenvironment and sensitivity to targeted therapy

Candido

Abrams

Steelman

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Various, diverse molecules contribute to the tumor microenvironment and influence invasion and metastasis. In this review, the roles of neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinase-9 (MMP-9) in the tumor microenvironment and sensitivity to therapy will be discussed. The lipocalin family of proteins has many important functions. For example when NGAL forms a complex with MMP-9 it increases its stability which is important in cancer metastasis. Small hydrophobic molecules are bound by NGAL which can alter their entry into and efflux from cells. Iron transport and storage are also influenced by NGAL activity. Regulation of iron levels is important for survival in the tumor microenvironment as well as metastasis. Innate immunity is also regulated by NGAL as it can have bacteriostatic properties. NGAL and MMP-9 expression may also affect the sensitivity of cancer cells to chemotherapy as well as targeted therapy. Thus NGAL and MMP-9 play important roles in key processes involved in metastasis as well as response to therapy. This article is part of a Special Issue entitled: Tumor Microenvironment Regulation of Cancer Cell Survival, Metastasis, Inflammation, and Immune Surveillance edited by Peter Ruvolo and Gregg L. Semenza.

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Section: Effects Of Ngal On Cancer Progressionmentioning

confidence: 99%

Section: Accepted Manuscriptmentioning

confidence: 99%

mentioning

confidence: 99%

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Roles of NGAL and MMP-9 in the tumor microenvironment and sensitivity to targeted therapy

Candido

Abrams

Steelman

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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“…Numerous experiments carried out in cellular and murine cancer models have also demonstrated a role of NGAL in cell migration and invasion (30)(31)(32).…”

Section: Chemotactic Role Of Ngalmentioning

confidence: 99%

More than a simple biomarker: the role of NGAL in cardiovascular and renal diseases

2018

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Neutrophil gelatinase-associated lipocalin (NGAL) is a small circulating protein that is highly modulated in a wide variety of pathological situations, making it a useful biomarker of various disease states. It is one of the best markers of acute kidney injury, as it is rapidly released after tubular damage. However, a growing body of evidence highlights an important role for NGAL beyond that of a biomarker of renal dysfunction. Indeed, numerous studies have demonstrated a role for NGAL in both cardiovascular and renal diseases. In the present review, we summarize current knowledge concerning the involvement of NGAL in cardiovascular and renal diseases and discuss the various mechanisms underlying its pathological implications.

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“…Cytokine array analysis between parent KYSE150 cells and LuM cells demonstrated that several cytokines were up-regulated in the supernatant of LuM cells compared with that of parent KYSE150 cells (Figure 3C, Table 1). Among these up-regulated proteins, we focused on LCN2, since it was previously shown to promote the migration and invasion of ESCC cells [12]. The expression level of LCN2 protein was higher in both the cell lysate and the supernatant of LuM cells than in those of parent KYSE150 cells (Figure 3D and 3E).…”

Section: Resultsmentioning

confidence: 98%

Subcloning and characterization of highly metastatic cells derived from human esophageal squamous cell carcinoma KYSE150 cells by in vivo selection

et al. 2017

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Esophageal cancer is the eighth most common cancer and the sixth most common cause of cancer-related deaths worldwide. Despite the research progress in understanding the disease, the mechanism underlying the metastasis is still unclear. Here, we successfully generated a highly metastatic cell subline, designated as KYSE150-LuM, derived from an esophageal squamous cell carcinoma cell line (KYSE150) by in vivo selection. To elucidate the mechanisms driving metastasis, we characterized the gene expression differences between LuM cells and parent KYSE150 cells. IL-6, IL-1β, and LCN2, previously associated with tumor growth and metastasis, were up-regulated in LuM cells. Recent studies on cancer have increasingly focused on the tumor microenvironment, from which these cytokines are released. The fact that these three cytokines (IL-6, IL-1β, LCN2) were up-regulated in LuM cells indicates that these highly metastatic cells obtained through in vivo selection will be a useful resource for further studies on elucidating the mechanisms underlying the tumor microenvironment which is associated with cytokine-related tumor growth and metastasis. Moreover, LuM cells could disseminate to the lung in shorter period of time in vivo, indicating their utility for in vivo experiments of metastasis and new therapeutic targets in a shorter period of time than currently possible.

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Lipocalin 2 promotes the migration and invasion of esophageal squamous cell carcinoma cells through a novel positive feedback loop

Cited by 33 publications

References 36 publications

Roles of NGAL and MMP-9 in the tumor microenvironment and sensitivity to targeted therapy

Roles of NGAL and MMP-9 in the tumor microenvironment and sensitivity to targeted therapy

More than a simple biomarker: the role of NGAL in cardiovascular and renal diseases

Subcloning and characterization of highly metastatic cells derived from human esophageal squamous cell carcinoma KYSE150 cells by in vivo selection

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